Dosulepin

Identification

Summary

Dosulepin is a tricyclic antidepressant commonly used only in patients for whom alternative therapies are ineffective due to its toxicity potential.

Generic Name

Dosulepin

DrugBank Accession Number

DB09167

Background

Dosulepin (INN, BAN) formerly known as dothiepin (USAN), is a tricyclic antidepressant with anxiolytic properties that is used in several European and South Asian countries, as well as Australia, South Africa, and New Zealand. It is not FDA-approved due to low therpeutic index and significant toxicity in overdose. Dosulepin inhibits the reuptake of biogenic amines, increasing available neurotransmitter levels at the synaptic cleft. The use of dosulepsin is only recommended in patients who are intolerant or unresponsive to alternative antidepressant therapies. Dosulepsin is a thio derivative of Amitriptyline with a similar efficacy to that of Amitriptyline, and also exhibits anticholinergic, antihistamine and central sedative properties ⁸. Its hydrochloride form is a common active ingredient in different drug formulations.

Type

Small Molecule

Groups

Approved

Structure

3D

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MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Dosulepin (DB09167)

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Weight

Average: 295.44
Monoisotopic: 295.139470854

Chemical Formula

C₁₉H₂₁NS

Synonyms

• (3E)-3-dibenzo[b,e]thiepin-11(6H)-ylidene-N,N-dimethylpropan-1-amine
• 11-(3-Dimethylaminopropylidene)-6,11-dihydrodibenzo(b,e)thiepin
• Dosulepin
• Dosulepina
• Dosulépine
• Dosulepinum
• Dothiepin
• trans-dothiepin

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Pharmacology

Indication

Indicated in the treatment of symptoms of depressive illness, especially where an anti-anxiety effect is required.

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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Treatment of	Anxiety		••••••••••••			••••••• •••• ••••••
Treatment of	Depression		••••••••••••			••••••• •••• ••••••
Treatment of	Depression		••••••••••••			••••••

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Pharmacodynamics

Dosulepin is a tricyclic antidepressant that interacts with various receptors and transporters. It is a monoamine reuptake inhibitor with approximately equal potency for noradrenaline and 5-HT that increases the availability of these neurotransmitters at the central synapses ⁸. The metabolites of dosulepin are shown to inhibit 5HT uptake by the human blood platelet ².

Mechanism of action

By binding to noradrenaline transporter (NAT) and serotonin transporter (SERT) in an equipotent manner and inhibiting the reuptake activity, dosulepin increases the free levels of noradrenaline and 5HT at the synaptic cleft. It is shown that the main metabolite northiaden is a more potent inhibitor of noradrenaline uptake than the parent drug ⁵.

Dosulepin displays affinity towards α2-adrenoceptors and to a lesser extent, α1-adrenoceptors ⁴. Inhibition of presynaptic α2-adrenoceptors by dosulepin facilitates noradrenaline release and further potentiates the antidepressant effects ⁵. It also downregulates central β-adrenoceptors by causing a decline in the number of receptors and reduces noradrenaline-induced cyclic AMP formation ^7,5. Dosulepin binds to 5HT1A and 5HT2A receptors in the cerebral cortex and hippocampus as an antagonist. 5HT1A receptors are autoreceptors that inhibit 5HT release and 5HT2A receptors are Gi/Go-coupled receptors that reduces dopamine release upon activation ⁶. Antagonism at 5HT2A receptors may also improve sleep patterns. Dosulepin also binds to muscarinic acetylcholine receptors and causes antimuscarinic side effects such as dry mouth. By acting as an antagonist at histamine type 1 (H1) receptors, dosulepin mediates a sedative effect.

Main metabolites northiaden, dothiepin sulphoxide and northiaden sulphoxide may also bind to 5HT, α2 and H1 receptors, although with less affinity compared to the parent drug ³.

Target	Actions	Organism
A5-hydroxytryptamine receptor 1A	antagonist	Humans
A5-hydroxytryptamine receptor 2A	antagonist	Humans
AHistamine H1 receptor	antagonist	Humans
AMuscarinic acetylcholine receptor M1	antagonist	Humans
AMuscarinic acetylcholine receptor M2	antagonist	Humans
AMuscarinic acetylcholine receptor M3	antagonist	Humans
AMuscarinic acetylcholine receptor M4	antagonist	Humans
AMuscarinic acetylcholine receptor M5	antagonist	Humans
AAlpha-2 adrenergic receptors	antagonist	Humans
AAlpha-1 adrenergic receptors	antagonist	Humans
ASodium-dependent noradrenaline transporter	inhibitor	Humans
ASodium-dependent serotonin transporter	inhibitor	Humans

Absorption

Dosulepin is well absorbed from the intestines to reach the peak plasma concentration of 37.6ng/mL at 2.18 hours (Tmax) following oral administration of 25mg ⁷. The steady state concentrations are variable among individuals due to dynamic relationship between the drug dose and plasma concentration ⁸.

Volume of distribution

The mean apparent Vd is approximately 45 L/kg after oral administration of 75mg dosulepin ². It crosses the blood-brain barrier to mediate its antidepressant actions and also crosses the placental barriers, with low concentration of the drug excreted in breast milk ⁸.

Protein binding

Approximately 84% of unchanged drug is bound to serum protein ⁸.

Metabolism

Dosulepin undergoes extensive hepatic metabolism, to form main metabolites N-demethylated derivative northiaden (desmethyldosulepin or northiaden) and dosulepin S-oxide. Northiaden S-oxide is among 12 basic metabolites that are found in urine. The metabolic pathways of dosulepin is thought to involve N-demethylation, S-oxidation and glucuronic acid conjugation ⁸.

Hover over products below to view reaction partners

• Dosulepin
  • Northiaden
    • Northiaden S-oxide
  • Dosulepin S-oxide

Route of elimination

Dosulepin is predominantly cleared via renal elimination, mainly in the form of metabolites. Renal excretion of dosulepin and its metabolites accounts for 50% - 60% of total elimination, and biliary/fecal excretion is about 15%-40% ⁷.

Half-life

The elimination half life is approximately 20.4 hours following oral administration of 25mg dosulepin ⁷.

Clearance

Oral clearance is approximately 1.36 L/kg * hr following a single oral dose of 75mg dosulepin ².

Adverse Effects

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Toxicity

High mortality is associated with overdose of dosulepin (>5mg/kg) with the onset of toxicity occuring within 4-6 hours. Dosulepin may increase the risk of cardiovascular toxicity (cardiac arrhythmias, conduction disorders, cardiac failure and circulatory collapse) and severe hypotension, especially in the elderly ⁷. Withdrawal symptoms are reported in case of sudden cessation of therapy, which include insomnia, irritability, headache, nausea, giddiness, panic-anxiety, extreme motor restlessness and excessive perspiration. There have been reports of increased suicidal thoughts or behaviour with dosulepin treatment. Oral lowest published toxic dose (Toxic Dose Low, TDLo) is 90 mg/kg in infants and 4.5 mg/kg in female adults. Intravenous LD50 in mouse is 31 mg/kg ^MSDS.

Most common adverse effects involve the central nervous system (drowsiness, extrapyramidal symptoms, tremor, confusional states, disorientation, dizziness, paraesthesia, alterations to EEG patterns), anticholinergic effects (dry mouth, sweating, urinary retention), cardiovascular system (hypotension, postural hypotension, tachycardia, palpitations, arrhythmias, conduction defects), endocrine system (altered libido), gastrointestinal system (nausea, vomiting, constipation) and blurred vision ⁸.

Pathways

Not Available

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Interactions

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This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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1,2-Benzodiazepine	The risk or severity of CNS depression can be increased when Dosulepin is combined with 1,2-Benzodiazepine.
Abametapir	The serum concentration of Dosulepin can be increased when it is combined with Abametapir.
Abatacept	The metabolism of Dosulepin can be increased when combined with Abatacept.
Abiraterone	The metabolism of Dosulepin can be decreased when combined with Abiraterone.
Abrocitinib	The metabolism of Abrocitinib can be decreased when combined with Dosulepin.

Food Interactions

Not Available

Products

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Product Ingredients

Ingredient	UNII	CAS	InChI Key
Dosulepin hydrochloride	3H0042311V	897-15-4	XUPZAARQDNSRJB-SJDTYFKWSA-N

International/Other Brands

Depropin (CCM Duopharma Biotech) / Dopress (Mylan) / Dothip (Micro Synapse) / Dothitab (Psycorem) / Dotopine (Shou Chan) / Elate (Crescent) / Espin (Taejoon Pharm) / Harmomed (Kwizda) / Othtric (Cubit) / Prothiaden (Abbott / Teofarma) / Qualiaden (Quality Pharm) / Singsong (Yuan Chou) / Thaden (Pharmacare) / Vick-Thiaden (Vickmans)

Categories

ATC Codes

N06AA16 — Dosulepin

• N06AA — Non-selective monoamine reuptake inhibitors
• N06A — ANTIDEPRESSANTS
• N06 — PSYCHOANALEPTICS
• N — NERVOUS SYSTEM

Drug Categories

• Adrenergic Agents
• Adrenergic Uptake Inhibitors
• Agents producing tachycardia
• Agents that produce hypertension
• Agents that reduce seizure threshold
• Anticholinergic Agents
• Antidepressive Agents
• Antidepressive Agents, Tricyclic
• Central Nervous System Agents
• Central Nervous System Depressants
• Combined Inhibitors of Serotonin/Norepinephrine Reuptake
• Cytochrome P-450 CYP1A2 Inhibitors
• Cytochrome P-450 CYP1A2 Inhibitors (moderate)
• Cytochrome P-450 CYP2B6 Substrates
• Cytochrome P-450 CYP2B6 Substrates with a Narrow Therapeutic Index
• Cytochrome P-450 CYP2C19 Inhibitors
• Cytochrome P-450 CYP2C19 inhibitors (strength unknown)
• Cytochrome P-450 CYP2C9 Inhibitors
• Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
• Cytochrome P-450 CYP2D6 Inhibitors
• Cytochrome P-450 CYP2D6 Inhibitors (moderate)
• Cytochrome P-450 CYP2D6 Inhibitors (weak)
• Cytochrome P-450 CYP2D6 Substrates
• Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index
• Cytochrome P-450 Enzyme Inhibitors
• Cytochrome P-450 Substrates
• Dibenzothiepins
• Heterocyclic Compounds, Fused-Ring
• Histamine Antagonists
• Histamine H1 Antagonists
• Membrane Transport Modulators
• Muscarinic Antagonists
• Narrow Therapeutic Index Drugs
• Nervous System
• Neurotoxic agents
• Neurotransmitter Agents
• Neurotransmitter Uptake Inhibitors
• Non-Selective Monoamine Reuptake Inhibitors
• Potential QTc-Prolonging Agents
• Psychoanaleptics
• Psychotropic Drugs
• QTc Prolonging Agents
• Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
• Serotonin 5-HT1 Receptor Antagonists
• Serotonin 5-HT1A Receptor Antagonists
• Serotonin 5-HT2 Receptor Antagonists
• Serotonin 5-HT2A Receptor Antagonists
• Serotonin Agents
• Serotonin Modulators
• Serotonin Receptor Antagonists
• Sulfur Compounds
• Tertiary amine tricyclic antidepressants
• Thiepins

Chemical TaxonomyProvided by Classyfire

Description

This compound belongs to the class of organic compounds known as dibenzothiepins. These are compounds containing a dibenzothiepin moiety, which consists of two benzene connected by a thiepine ring.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Benzothiepins

Sub Class

Dibenzothiepins

Direct Parent

Dibenzothiepins

Alternative Parents

Alkylarylthioethers / Benzenoids / Trialkylamines / Organopnictogen compounds / Hydrocarbon derivatives

Substituents

Alkylarylthioether / Amine / Aromatic heteropolycyclic compound / Aryl thioether / Benzenoid / Dibenzothiepin / Hydrocarbon derivative / Organic nitrogen compound / Organonitrogen compound / Organopnictogen compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

dothiepin (CHEBI:36803)

Affected organisms

Not Available

Chemical Identifiers

UNII

W13O82Z7HL

CAS number

113-53-1

InChI Key

PHTUQLWOUWZIMZ-GZTJUZNOSA-N

InChI

InChI=1S/C19H21NS/c1-20(2)13-7-11-17-16-9-4-3-8-15(16)14-21-19-12-6-5-10-18(17)19/h3-6,8-12H,7,13-14H2,1-2H3/b17-11+

IUPAC Name

dimethyl({3-[(2E)-9-thiatricyclo[9.4.0.0³,⁸]pentadeca-1(15),3,5,7,11,13-hexaen-2-ylidene]propyl})amine

SMILES

CN(C)CC\C=C1/C2=CC=CC=C2CSC2=CC=CC=C12

References

General References

1. Lancaster SG, Gonzalez JP: Dothiepin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness. Drugs. 1989 Jul;38(1):123-47. [Article]
2. Maguire KP, Burrows GD, Norman TR, Scoggins BA: Metabolism and pharmacokinetics of dothiepin. Br J Clin Pharmacol. 1981 Sep;12(3):405-9. [Article]
3. Fulton A, Norman TR, Cheng H, Burrows GD: Assessment of the antidepressant activity of dothiepin and its metabolites by preclinical tests. J Affect Disord. 1982 Sep;4(3):261-9. [Article]
4. Gillman PK: Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30. [Article]
5. Heal D, Cheetham S, Martin K, Browning J, Luscombe G, Buckett R: Comparative pharmacology of dothiepin, its metabolites, and other antidepressant drugs Drug Development Research. 1992 May 1;27(2):121–135. [Article]
6. 45. (2012). In Rang and Dale's Pharmacology (7th ed., pp. 559). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
7. Co-pharma Ltd. SUMMARY OF PRODUCT CHARACTERISTICS: Dosulepin hydrochloride tablets [Link]
8. Alphapharm: DOTHEP (Dothiepin hydrochloride) Product information [Link]

External Links

KEGG Drug

D07872

PubChem Compound

5284550

PubChem Substance

310265076

ChemSpider

4447605

RxNav

3634

ChEBI

36803

ChEMBL

CHEMBL1492500

ZINC

ZINC000000020249

Wikipedia

Dosulepin

MSDS

Download (599 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
Not Available	Completed	Not Available	Depressive Episodes	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Tablet	Oral
Capsule	Oral	25 MG
Pill
Tablet, film coated

Prices

Not Available

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	131- 134.6	MSDS
boiling point (°C)	339.8- 341.6	MSDS
water solubility	Partly miscible	MSDS

Predicted Properties

Property	Value	Source
Water Solubility	0.000572 mg/mL	ALOGPS
logP	4.98	ALOGPS
logP	4.52	Chemaxon
logS	-5.7	ALOGPS
pKa (Strongest Basic)	9.76	Chemaxon
Physiological Charge	1	Chemaxon
Hydrogen Acceptor Count	1	Chemaxon
Hydrogen Donor Count	0	Chemaxon
Polar Surface Area	3.24 Å2	Chemaxon
Rotatable Bond Count	3	Chemaxon
Refractivity	104.59 m3·mol-1	Chemaxon
Polarizability	34.57 Å3	Chemaxon
Number of Rings	3	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	Yes	Chemaxon
Ghose Filter	Yes	Chemaxon
Veber's Rule	Yes	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Not Available

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0f6t-0090000000-866fdc86f1e3621cada4
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0006-1090000000-7b40f8137a87d1b068ed
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0udi-1090000000-52c87a903497bc2c4571
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0006-0090000000-7debc4af2cfd1efcfa86
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-00di-0290000000-c793130d7223e627858f
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0006-5590000000-a4f25891d1f51c65b6e2
Predicted 1H NMR Spectrum	1D NMR	Not Applicable
Predicted 13C NMR Spectrum	1D NMR	Not Applicable

Chromatographic Properties

Collision Cross Sections (CCS)

Adduct	CCS Value (Å2)	Source type	Source
[M-H]-	181.5169306	predicted	DarkChem Lite v0.1.0
[M-H]-	167.1736	predicted	DeepCCS 1.0 (2019)
[M+H]+	182.2414306	predicted	DarkChem Lite v0.1.0
[M+H]+	169.5316	predicted	DeepCCS 1.0 (2019)
[M+Na]+	181.6357306	predicted	DarkChem Lite v0.1.0
[M+Na]+	175.62474	predicted	DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.

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Details1. 5-hydroxytryptamine receptor 1A

Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Antagonist

General Function

Serotonin receptor activity

Specific Function

G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers...

Gene Name

HTR1A

Uniprot ID

P08908

Uniprot Name

5-hydroxytryptamine receptor 1A

Molecular Weight

46106.335 Da

References

1. Fulton A, Norman TR, Cheng H, Burrows GD: Assessment of the antidepressant activity of dothiepin and its metabolites by preclinical tests. J Affect Disord. 1982 Sep;4(3):261-9. [Article]

Details2. 5-hydroxytryptamine receptor 2A

Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Antagonist

General Function

Virus receptor activity

Specific Function

G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...

Gene Name

HTR2A

Uniprot ID

P28223

Uniprot Name

5-hydroxytryptamine receptor 2A

Molecular Weight

52602.58 Da

References

1. Fulton A, Norman TR, Cheng H, Burrows GD: Assessment of the antidepressant activity of dothiepin and its metabolites by preclinical tests. J Affect Disord. 1982 Sep;4(3):261-9. [Article]

Details3. Histamine H1 receptor

Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Antagonist

General Function

Histamine receptor activity

Specific Function

In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...

Gene Name

HRH1

Uniprot ID

P35367

Uniprot Name

Histamine H1 receptor

Molecular Weight

55783.61 Da

References

1. Gillman PK: Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30. [Article]

Details4. Muscarinic acetylcholine receptor M1

Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Antagonist

General Function

Phosphatidylinositol phospholipase c activity

Specific Function

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...

Gene Name

CHRM1

Uniprot ID

P11229

Uniprot Name

Muscarinic acetylcholine receptor M1

Molecular Weight

51420.375 Da

References

1. Gillman PK: Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30. [Article]

Details5. Muscarinic acetylcholine receptor M2

Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Antagonist

General Function

G-protein coupled acetylcholine receptor activity

Specific Function

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...

Gene Name

CHRM2

Uniprot ID

P08172

Uniprot Name

Muscarinic acetylcholine receptor M2

Molecular Weight

51714.605 Da

References

1. Gillman PK: Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30. [Article]

Details6. Muscarinic acetylcholine receptor M3

Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Antagonist

General Function

Receptor activity

Specific Function

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...

Gene Name

CHRM3

Uniprot ID

P20309

Uniprot Name

Muscarinic acetylcholine receptor M3

Molecular Weight

66127.445 Da

References

1. Gillman PK: Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30. [Article]

Details7. Muscarinic acetylcholine receptor M4

Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Antagonist

General Function

Guanyl-nucleotide exchange factor activity

Specific Function

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...

Gene Name

CHRM4

Uniprot ID

P08173

Uniprot Name

Muscarinic acetylcholine receptor M4

Molecular Weight

53048.65 Da

References

1. Gillman PK: Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30. [Article]

Details8. Muscarinic acetylcholine receptor M5

Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Antagonist

General Function

Phosphatidylinositol phospholipase c activity

Specific Function

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...

Gene Name

CHRM5

Uniprot ID

P08912

Uniprot Name

Muscarinic acetylcholine receptor M5

Molecular Weight

60073.205 Da

References

1. Gillman PK: Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30. [Article]

Details9. Alpha-2 adrenergic receptors (Protein Group)

Kind

Protein group

Organism

Humans

Pharmacological action

Yes

Actions

Antagonist

General Function

Thioesterase binding

Specific Function

Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...

---

Components:

Name	UniProt ID
Alpha-2A adrenergic receptor	P08913
Alpha-2B adrenergic receptor	P18089
Alpha-2C adrenergic receptor	P18825

References

1. Heal D, Cheetham S, Martin K, Browning J, Luscombe G, Buckett R: Comparative pharmacology of dothiepin, its metabolites, and other antidepressant drugs Drug Development Research. 1992 May 1;27(2):121–135. [Article]

Details10. Alpha-1 adrenergic receptors (Protein Group)

Kind

Protein group

Organism

Humans

Pharmacological action

Yes

Actions

Antagonist

General Function

Protein heterodimerization activity

Specific Function

This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...

---

Components:

Name	UniProt ID
Alpha-1A adrenergic receptor	P35348
Alpha-1B adrenergic receptor	P35368
Alpha-1D adrenergic receptor	P25100

References

1. Heal D, Cheetham S, Martin K, Browning J, Luscombe G, Buckett R: Comparative pharmacology of dothiepin, its metabolites, and other antidepressant drugs Drug Development Research. 1992 May 1;27(2):121–135. [Article]

Details11. Sodium-dependent noradrenaline transporter

Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Inhibitor

General Function

Norepinephrine:sodium symporter activity

Specific Function

Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.

Gene Name

SLC6A2

Uniprot ID

P23975

Uniprot Name

Sodium-dependent noradrenaline transporter

Molecular Weight

69331.42 Da

References

1. Gillman PK: Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30. [Article]
2. Wille SM, Cooreman SG, Neels HM, Lambert WE: Relevant issues in the monitoring and the toxicology of antidepressants. Crit Rev Clin Lab Sci. 2008;45(1):25-89. doi: 10.1080/10408360701713112 . [Article]

Details12. Sodium-dependent serotonin transporter

Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Inhibitor

General Function

Serotonin:sodium symporter activity

Specific Function

Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into t...

Gene Name

SLC6A4

Uniprot ID

P31645

Uniprot Name

Sodium-dependent serotonin transporter

Molecular Weight

70324.165 Da

References

1. Gillman PK: Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30. [Article]
2. Wille SM, Cooreman SG, Neels HM, Lambert WE: Relevant issues in the monitoring and the toxicology of antidepressants. Crit Rev Clin Lab Sci. 2008;45(1):25-89. doi: 10.1080/10408360701713112 . [Article]

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Drug created at October 13, 2015 23:52 / Updated at May 07, 2021 21:06